The metabolically-mediated toxicity of halogenated aromatic pollutants (polyhalogenated biphenyls, benzenes, naphthalenes and p-terphenyls) depends on a variety of factors which include the nature of the halogen atom, the nature of the aromatic nucleus, the position and number of the halogen atoms and the source of the drug-metabolizing enzymes. This project will initially focus on determining the effects of structure on the microsomal-enzyme mediated metabolism of selected aromatic and halogenated aromatic substrates. In addition the metabolic studies will also be determined using Chinese hamster ovary (CHO) cells in the presence and absence of exogenous microsomal enzymes. These experiments will focus on the factors which influence the formation of phase I metabolites and covalently bound halogenated aromatic-macromolecular (DNA, RNA and protein) adducts. Using a similar approach the effects of halogenated aromatics in mutating CHO cells to 8-azaguanine resistant mutants will also be determined. The effects of structure on the pharmacodynamics of halogenated aromatics suggests that in the PCB series there is a preferential retention of the more highly halogenated congeners and PCBs which are relatively lower in their degree of ortho chloro. Group model studies will be undertaken to determine a suitable mammalian system which can be used as a model for humans.